PT - JOURNAL ARTICLE AU - Joshua Meier AU - Roshan Rao AU - Robert Verkuil AU - Jason Liu AU - Tom Sercu AU - Alexander Rives TI - Language models enable zero-shot prediction of the effects of mutations on protein function AID - 10.1101/2021.07.09.450648 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.07.09.450648 4099 - http://biorxiv.org/content/early/2021/07/10/2021.07.09.450648.short 4100 - http://biorxiv.org/content/early/2021/07/10/2021.07.09.450648.full AB - Modeling the effect of sequence variation on function is a fundamental problem for understanding and designing proteins. Since evolution encodes information about function into patterns in protein sequences, unsupervised models of variant effects can be learned from sequence data. The approach to date has been to fit a model to a family of related sequences. The conventional setting is limited, since a new model must be trained for each prediction task. We show that using only zero-shot inference, without any supervision from experimental data or additional training, protein language models capture the functional effects of sequence variation, performing at state-of-the-art.Competing Interest StatementThe authors have declared no competing interest.